In the process of producing radiotracers for PET, a medical molecular imaging method, radionucleids, such as 18F must be extracted from the cyclotron target content and transferred into a solvent for the radiochemical labeling reaction. Besides ion exchangers, an electrochemical method can be applied. In a first step, the 18F ions in a solution with a first solvent, e.g. 18O-enriched water, flows past a pair of graphite or glassy carbon electrodes across which a potential is applied. The 18F ions are deposited on the positively-charged capture electrode (the anode). In a second step, the first solvent is exchanged with a suitable solvent, e.g. DMSO, and a reverse potential is applied to release the ions from the capture electrode back into the solution. The second solution is then transferred to a separations system for labeling.
If a release voltage is applied during the second step, fluoride gets trapped on the counter electrode (i.e., the anode after reversing the potential or the cathode during the first step) while the fluoride is released into solution from the first electrode by application of the reverse potential. The fluoride is electrophoretically driven to the counter electrode and readsorbed thereon. In order to prevent counter trapping of 18F on the cathode, platinum electrodes have been used, as platinum is known for its low fluoride adsorption.
Known processes and structures for trapping and release of 18F− do trap and release 18F− but do not ensure that the released 18F− is suitable for a labeling reaction. Specifically, the labeling yield may be low or zero in some cases. One reason could be that high voltages applied during the process create other ions which later then compete with the released 18F ions to bind to the provided precursor.
To limit counter trapping, the prior art methods employ one carbon capture electrode and a noble metal counter electrode. The prior art counter electrode is typically formed from a metal, e.g. platinum, to prevent re-adsorption of the radionucleids during the release process applying a reverse potential. Platinum has poor absorption/adsorption properties for fluoride ions.
Whether formed from platinum or solid graphite or glassy carbon plate, the electrodes of the prior art provide several challenges. They are very expensive, hard to machine and hard to integrate into a mass manufacturable process such as injection molding. For example, the prior art has used monolithic glassy carbon plates for the electrodes. However, these are very expensive, costing about $250 for a 25×25×3 mm3 piece, and are also difficult to machine and complex to integrate into a disposable product.
WO 2009/015048 A2 describes coin-shaped and long-channel shaped electrochemical cells utilizing metal, graphite, silicon, and polymer composites of these materials. The document describes that the precursor is introduced into the cell and that gas drying is achieved with heating and acetonitrile drying. The operation is described as employing potentials up to 500V.
WO 2008/028260 A2 describes electrochemical phase transfer devices consisting of a fine network of carbon filaments. An electrical double layer is used for capture, making it possible to trap 18F− without applying an external voltage. Cold Acetonitrile is listed as a method for drying. No or low externally applied voltage minimizes REDOX reactions. Heating is described for improving release of the trapped ions.
Both WO 2008/028260 A2 and WO 2009/015048 A2 describe the use of alternating currents during the step of releasing of the fluoride.
There is therefore a need for a disposable electrochemical phase transfer reactor which may be easily produced while still providing sufficient operating efficiencies. The integration of solid glassy carbon plates into a disposable phase transfer unit is complex due to the high cost of the glassy carbon, the need to CNC machine the glassy carbon, the poor ability of the glassy carbon to bond to plastics, and the difficulty of maintaining the glassy carbon microstructures free of leaks. There is also a need for a method of performing electrochemical phase transfer which provides an acceptable yield of a labeling ion which will attach to a precursor.